Novel POLG mutation in a patient with sensory ataxia, neuropathy, ophthalmoparesis and stroke
| Autor: | Man-Mut Yau, Wai-Kwan Siu, Cheuk-Wing Fung, Chloe Miu Mak, Hencher Han-Chih Lee, Chun-Yiu Law, Ching-Wan Lam, Kwai-Fun Huen |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Adolescent Mitochondrial disease Clinical Biochemistry Encephalopathy DNA-Directed DNA Polymerase Compound heterozygosity MELAS syndrome Biochemistry Ophthalmoparesis Polyneuropathies Sensory ataxia Mitochondrial myopathy medicine Humans Ophthalmoplegia Cortical blindness business.industry Biochemistry (medical) General Medicine medicine.disease DNA Polymerase gamma Stroke Mutation Ataxia Female medicine.symptom business |
| Zdroj: | Clinica Chimica Acta. 448:211-214 |
| ISSN: | 0009-8981 |
| DOI: | 10.1016/j.cca.2015.06.028 |
| Popis: | Background Clinical diagnosis of POLG-related disorders can be challenging because the phenotypic spectrums are heterogeneous which can mimic different types of mitochondrial disorders. Case We report a case of POLG-related disorder in an 18 y Chinese girl who had been diagnosed as MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) for the past 8 y. She first presented at 10 y with sudden onset of headache, repeated focal seizures and visual loss, complicated with residual sensory and motor neuropathy, ophthalmoparesis and cortical blindness. MRI brain showed extensive cytotoxic edema and ischemia in bilateral parietal–occipital lobes. Mutation analysis for common point mutations in the mitochondrial DNA and muscle biopsy was negative. She was referred to us for mitochondrial whole genome analysis. However, no pathogenic variants can be determined. We initiated further genetic analysis for POLG which confirmed compound heterozygous mutations NM_002693.2 :c.925C>T (p.Arg309Cys) and a novel mutation c.2244G>T (p.Trp748Cys). Both were determined to be pathogenic using in silico analysis. Conclusions The novel mutation contributes to the expanding spectrum of disease-causing mutations. A definitive diagnosis can benefit our patient and also the relatives by avoiding sodium valproate induced liver toxicity in POLG patients and also the heterozygotes. |
| Databáze: | OpenAIRE |
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